CN113244446B - Magnesium alloy composite material and preparation method and application thereof - Google Patents
Magnesium alloy composite material and preparation method and application thereof Download PDFInfo
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
- C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
- A61L2300/604—Biodegradation
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/622—Microcapsules
Abstract
The invention discloses a magnesium alloy composite material and a preparation method and application thereof, wherein the magnesium alloy composite material comprises a matrix; drug-loaded nano microspheres are distributed on the surface of the matrix; the matrix and the drug-loaded nano-microspheres are coated in alginate; wherein the matrix comprises a magnesium matrix; the magnesium substrate is of a surface porous structure; the drug-loaded nano-microspheres comprise drugs and polyester nano-microspheres; the medicine is coated in the polyester nano-microsphere. The magnesium matrix with excellent biocompatibility and bioactivity is combined with the drug-loaded nano-microspheres with drug slow release and tissue repair effects to form the magnesium alloy composite material; the magnesium alloy composite material not only has a surface porous structure, but also has good drug release performance and tissue regeneration induction capability, and effectively promotes the repair and reconstruction of tissues.
Description
Technical Field
The invention relates to the field of biomedical materials, in particular to a magnesium alloy composite material and a preparation method and application thereof.
Background
More than 300 million patients with bone defects and bone injuries per year in China have large demand on bone repair products. According to data of Chinese medical instrument blue book, the market scale of the orthopaedic implantation medical instrument in China in 2019 is 304 hundred million yuan, which is listed second in the world. However, most of the existing tissue repair materials lack biological activity, only can play a role in simply filling or supporting tissues, and are difficult to meet clinical requirements. With the development of tissue repair towards regeneration and reconstruction, restoration of biological functions, and the like, the tissue repair material industry is revolutionarily changed, and particularly, biomedical materials capable of inducing tissue regeneration or reconstruction have become an important development direction and an inevitable trend.
The ideal bone reconstruction material should meet the requirements of light weight, accurate mechanical matching, high biological activity, capability of inducing autologous tissue and revascularization, controllable degradation and the like. Magnesium and its alloy are the metal materials which are recognized as degradable clinically and have better biocompatibility, have the advantages of low density, promotion of osteogenesis, induction of bone growth and the like, and gradually expose the head and horn in the field of tissue repair. In the related technology, the application of the magnesium and the magnesium alloy implant mainly takes materials for intraosseous fixation as main materials, and teaches personalized functional reconstruction and repair of tissue defects such as bone tissues and the like; in order to realize breakthrough of magnesium alloy materials in application, the following key problems need to be overcome: the magnesium alloy prepared by the traditional processing mode lacks the capability of effectively inducing tissue regeneration and is difficult to meet the requirement of precise medical treatment.
With the continuous development of medical science, pharmacy, biomedical engineering and other disciplines, drugs aiming at tissue repair including bioactive macromolecular drugs are not uncommon, but the problem of sustained and stable release of the drugs in vivo is still difficult to solve. Whether the medicine is orally taken or injected intravenously, the change of the blood concentration can generate a peak-valley phenomenon, the medicine concentration is too high to cause larger toxic and side effects, and the treatment effect cannot be achieved if the medicine concentration is too low. The calcium silicate has excellent biocompatibility, bioactivity and degradability, and is a novel bone repair material; and when the calcium silicate is degraded, the surrounding environment is slightly alkaline, which is beneficial to the growth of cells. Polyester microspheres generally refer to polyester aggregates having a diameter on the nanometer to micrometer scale and a spherical shape. The degradable polyester-based microspheres have simple synthesis process, controllable degradation and easy performance expansion, and are widely used as controlled release carriers of tissue engineering. However, due to the size, dispersibility and the like of the drug-loaded microsphere particles, the drug-loaded microsphere is not suitable for being used in the tissue repair occasion independently.
The magnesium-containing composite microspheres/scaffolds prepared by the related art generally have the following problems:
1) Due to the size, the dispersibility and the like of the drug-carrying microsphere particles, the drug-carrying microsphere is not suitable for being used in tissue repair occasions independently;
2) The drug-loaded microspheres are large in size, and the hollow magnesium sample must be obtained first to effectively load the drug-loaded microspheres, so that the mechanical strength of the magnesium sample is low;
3) The magnesium-containing bone cement serving as a matrix material has high brittleness and potential safety hazard in application;
4) The preparation process of the material is complex and difficult to industrialize.
Therefore, there is a need to develop a magnesium alloy composite material having good drug release performance and tissue regeneration inducing ability.
Disclosure of Invention
The first technical problem to be solved by the invention is as follows: provides a magnesium alloy composite material which has good drug release performance and tissue regeneration induction capability.
The second technical problem to be solved by the invention is as follows: provides a preparation method of the magnesium alloy composite material.
The third technical problem to be solved by the invention is: provides the application of the magnesium alloy composite material.
In order to solve the first technical problem, the technical scheme provided by the invention is as follows: a magnesium alloy composite material comprises a substrate;
drug-loaded nano microspheres are distributed on the surface of the matrix;
the matrix and the drug-loaded nano-microspheres are coated in alginate;
wherein the matrix comprises a magnesium matrix;
the magnesium substrate is of a surface porous structure;
the drug-loaded nano-microspheres comprise drugs and polyester nano-microspheres;
the medicine is coated in the polyester nano-microsphere.
After magnesium is treated by using a plasma electrolytic oxidation technology, a coating with a porous structure is formed on the surface of the magnesium; the polyester nano microspheres are mainly distributed in the pores on the surface of the magnesium alloy, so that the microspheres can be embedded into the pores on the surface of the magnesium alloy, and the microspheres can be firmly attached to the surface of the magnesium.
According to some embodiments of the invention, the method of preparing the magnesium matrix comprises a plasma electrolytic oxidation process; preferably, the mass content of magnesium in the magnesium matrix is more than 99%; preferably, the preparation method of the drug-loaded nano-microsphere comprises an emulsion solvent volatilization method.
After magnesium is treated by using a plasma electrolytic oxidation technology, a porous structure coating formed on the surface of magnesium can be firmly attached to the surface of a magnesium matrix, and the effect of inhibiting the degradation of the magnesium matrix is mainly achieved; meanwhile, the nano microspheres are distributed in the pores of the porous structure coating, so that the pores of the porous structure coating are reduced, and the degradation of a magnesium matrix is further inhibited; the medicine loaded by the nano-microspheres can be slowly released to act on the surrounding environment; and finally, coating a layer of alginate on the surfaces of the matrix and the drug-loaded nano microspheres, so that the microspheres can be further firmly fixed on the surface of the magnesium matrix, and the coating can also inhibit the degradation of the magnesium matrix.
According to some embodiments of the invention, the polyester nanospheres, the starting material for preparation, comprise polyester; preferably, the polyester comprises at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, poly 3-hydroxyalkanoate, poly (3-hydroxybutyrate), poly 3-hydroxybutyrate-co-3-hydroxyvalerate, polytrimethylene carbonate, and polybutylene succinate; preferably, the molecular weight of the polyester is 1.0-10.0 kilodalton; more preferably, the particle size of the drug-loaded nano-microsphere is 50 nm-400 nm.
Polyester microspheres generally refer to polyester aggregates having a diameter on the nanometer to micrometer scale and a spherical shape. The degradable polyester-based microspheres have the advantages of simple synthesis process, controllable degradation and easy performance expansion, and are widely used as controlled release carriers for tissue engineering.
According to some embodiments of the invention, the medicament comprises one of bone morphogenetic protein-2 (BMP-2), bone morphogenetic protein-7 (BMP-7), interleukin-4 (IL-4), vascular Endothelial Growth Factor (VEGF), alendronate sodium, naringin, and resveratrol; preferably, the mass ratio of the medicine to the polyester nano-microspheres is 1:5-100; preferably, the release period of the drug is 14 to 28 days.
According to some embodiments of the invention, the alginate comprises sodium alginate; preferably, the alginate has a viscosity of 10 to 1000 mPa.s.
The magnesium alloy composite material according to the embodiment of the invention has at least the following beneficial effects: the matrix material of the magnesium alloy composite material adopts magnesium, has excellent biocompatibility and bioactivity, has the advantages of small density, capability of promoting osteogenesis and inducing bone growth, and can be used as an induction template for providing structural, mechanical and biological signals to guide survival, proliferation and correct differentiation of bone-related cells. The stent drug-loaded nano-microsphere is prepared from polyester (degradable), has strong drug controlled release capacity, and is more suitable for treating diseases such as tissue defect, bacterial infection, inflammation, tumor and the like. Through the introduction of the drug-loaded nano-microspheres and the alginate coating, the drug release is controlled, and the degradation of magnesium can be inhibited. The drug-loaded polyester nano-microsphere provided by the invention is simple in combination mode with a magnesium matrix and easy to prepare.
To solve the second technical problem, the present invention provides the following technical solutions: the preparation method of the magnesium alloy composite material comprises the following steps: the method comprises the following steps: and loading the drug-loaded nano microspheres on the surface of the matrix, and then coating the matrix with alginate.
According to some embodiments of the invention, the method further comprises performing plasma electrolytic oxidation on the matrix before loading the drug-loaded nano-microspheres.
According to some embodiments of the invention, the plasma electrolytic oxidation comprises the steps of:
s1, carrying out surface treatment on pure magnesium to prepare a pure magnesium sample;
s2, carrying out plasma electrolytic oxidation on the pure magnesium sample in an electrolyte to prepare the magnesium matrix;
the electrolyte comprises the following raw materials in parts by weight: solution i and solution ii:
the solution I comprises the following raw materials in parts by weight: 12 to 14 portions of sodium phosphate, 1 to 5 portions of calcium hydroxide and 400 to 900 portions of water;
the solution II comprises the following raw materials in parts by weight: 2 to 9 portions of strontium hydroxide and 300 to 800 portions of water.
Plasma Electrolytic Oxidation (PEO) is the most practical and effective method to improve the corrosion resistance of magnesium alloys. The coating produced by adopting the PEO technology has the characteristics of economy, corrosion resistance, high hardness, good adhesive force and the like.
According to some embodiments of the invention, the volume ratio of solution i to solution ii is 0.9 to 1.1.
According to some embodiments of the invention, the parameters of the plasma electrolytic oxidation are as follows:
the frequency is 2000Hz; duty cycle 20%; the voltage is 500V; the temperature is 50-90 ℃; pre-oxidation current density 0.01A/cm 2 ～0.04A/cm 2 (ii) a The pre-oxidation time is 10-75 s; oxidation current 0.8A/cm 2 ～1.5A/cm 2 (ii) a The oxidation time is 6-20 min.
According to some embodiments of the invention, the plasma electrolytic oxidation is performed in a plasma electrolytic oxidation device.
According to some embodiments of the invention, the plasma electrolytic oxidation device is comprised of a pulsed dc power supply, an anode, a cathode, and an agitated cooling system.
According to some embodiments of the invention, the pure magnesium sample is connected to an anode.
According to some embodiments of the invention, the cathode comprises stainless steel.
According to some embodiments of the invention, the preparation method of the drug-loaded nano-microsphere comprises an emulsion solvent evaporation method.
According to some embodiments of the invention, the emulsion solvent evaporation process comprises the steps of:
s01, adding polyester into a solvent; preparing a polyester solution; dispersing the medicine in a polyester solution to prepare a primary emulsion;
s02, distributing the primary emulsion and a surfactant solution on two sides of the SPG membrane; stirring to obtain the drug-loaded nano-microsphere.
The emulsion solvent volatilization method has the advantages of simple and convenient operation, wide and adjustable experimental temperature, capability of preparing drug-loaded microspheres loaded with various drugs and the like.
According to some embodiments of the invention, the solvent comprises at least one of ethyl acetate, dichloromethane, chloroform and tetrahydrofuran.
According to some embodiments of the invention, the mass to volume ratio of polyester to solvent is 1g:10L to 20L.
According to some embodiments of the invention, the ratio by volume of the primary emulsion to the surfactant solution is from 1.
According to some embodiments of the invention, the surfactant comprises at least one of cellulose acetate, gelatin, methyl cellulose and polyvinyl alcohol.
The mass concentration of the surfactant solution is 0.5-1.5%.
According to some embodiments of the invention, the SPG membrane is a porous glass membrane.
According to some embodiments of the invention, the alginate is coated, comprising the steps of:
s001, adding the magnesium matrix into the suspension of the drug-loaded nano-microspheres, reacting for 4-20 h at 30-60 ℃, and drying after reaction to obtain the drug-loaded nano-microspheres loaded magnesium matrix;
s002, preparing the alginate into an alginate solution, and dropwise adding the alginate solution to the surface of the drug-loaded nano microsphere loaded magnesium matrix to prepare a coating precursor;
s003, adding the coating precursor into a calcium-containing solution to react for 0.5 to 3 hours, and drying after the reaction to prepare the magnesium alloy composite material;
the mass concentration of the alginate solution is 0.5 g/mL-8 g/mL;
the molar concentration of calcium in the calcium-containing solution is 0.2-4 mol/L.
According to some embodiments of the invention, the drug-loaded nanosphere suspension consists of the drug-loaded nanospheres and water.
According to the application of the embodiment of the invention, at least the following beneficial effects are achieved: the preparation method has low requirements on equipment, industrialized raw materials are available, the cost is low, and industrialization is easy to realize.
In order to solve the third technical problem, the technical scheme provided by the invention is as follows: the magnesium alloy composite material is applied to the preparation of a magnesium bracket.
According to another technical scheme of the invention: the magnesium scaffold is applied to tissue repair and regeneration materials.
According to the application of the embodiment of the invention, at least the following beneficial effects are achieved: the magnesium stent of the invention keeps good biocompatibility, realizes the sustained and controlled release of the drug, and is more suitable for the repair and regeneration of tissues.
Drawings
FIG. 1 is a graph comparing the in vitro drug release performance of magnesium stents prepared in examples 1 to 5 of the present invention and comparative examples 1 to 4;
FIG. 2 is an SEM photograph of pure magnesium in example 1 of the present invention;
FIG. 3 is an SEM photograph of a magnesium substrate in example 1 of the present invention.
Detailed Description
The idea of the invention and the resulting technical effects will be clearly and completely described below in connection with the embodiments, so that the objects, features and effects of the invention can be fully understood. It is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments, and other embodiments obtained by those skilled in the art without inventive efforts are within the protection scope of the present invention based on the embodiments of the present invention.
The purity of the pure magnesium selected by the invention is more than 99.9 percent.
The pure magnesium manufacturer is selected from Shanxi West Hongfu magnesium industry, beijing Global Jinding technology, inc. and Peak Longhai magnesium metal processing, inc.
Example 1 of the present invention is: a preparation method of a magnesium stent comprises the following steps:
s1, preparing a magnesium matrix:
pure magnesium (Shanxi Wen fond of hong Fu Mg industry, ltd.) was polished with 600-grit SiC sandpaper, then rinsed with deionized water for 3min, dehydrated with ethanol for 4min, and immediately dried in air to obtain a pure magnesium sample.
Under magnetic stirring, 15g of Na 3 PO 4 ·12H 2 O、2g Ca(OH) 2 Dissolving in 500mL of deionized water to obtain a solution I; 5g of Sr (OH) 2 ·8H 2 Dissolving O in 700mL of deionized water to obtain a solution II; and mixing the solution I and the solution II, and mechanically stirring for 40min to obtain the electrolyte.
The plasma electrolytic oxidation device consists of a pulse direct current power supply, a stainless steel container serving as a counter electrode and a stirring cooling system. The pure magnesium sample was connected to the anode output and immersed in the electrolyte, and the stainless steel container was connected to the cathode output of the power supply as the cathode. The stainless steel container is put into the plastic box, and water is injected between the stainless steel container and the plastic box to absorb heat.
Plasma electrolytic oxidation: constant current mode with frequency of 2000Hz, duty ratio of 20%, positive voltage of 500V, temperature of 75 deg.C, stirring, and current density of 0.02A/cm 2 Treating for 30s at a current density of 1A/cm 2 The treatment is carried out for 12min.
After plasma electrolytic oxidation treatment, washing for 3 times by using ethanol and deionized water, and performing air flow drying at room temperature (20-25 ℃) to obtain the magnesium matrix with the surface porous structure.
S2, preparing medicine-carrying nano microspheres:
dissolving 100mg of alendronate sodium in 0.1mL of water to obtain an alendronate sodium water solution; dissolving 0.5g of polylactic acid-glycolic acid copolymer (molecular weight: 3 ten thousand) in 5mL of dichloromethane to obtain polylactic acid-glycolic acid copolymer solution; uniformly dispersing the alendronate sodium aqueous solution in the polylactic acid-glycolic acid copolymer solution to obtain a primary emulsion.
Transferring the primary emulsion into a storage tank of an SPG membrane emulsifier, and allowing the primary emulsion to enter 300mL of aqueous solution dissolved with 3g of polyvinyl alcohol 1799 (Sigma) through membrane pores of an SPG membrane under the action of air/nitrogen pressure; stirring for 12h at 250rpm, centrifugally collecting the drug-loaded nano-microspheres, washing the drug-loaded nano-microspheres with deionized water for 5 times, and then adding 50mL of deionized water to obtain a drug-loaded nano-microsphere suspension with the particle size of 100 nm-200 nm.
S3, preparing a magnesium scaffold:
and (3) soaking the magnesium matrix in 40mL of medicine-carrying nano microsphere suspension at 45 ℃, and after 16 hours, carrying out freeze drying treatment on the sample to prepare the medicine-carrying nano microsphere loaded magnesium matrix.
Preparing a sodium alginate (viscosity: 100mpa · s-200 mpa · s) solution with the mass volume ratio of 2%, and uniformly dropwise adding (60 uL/s) 3mL of the sodium alginate solution onto the surface of the drug-loaded nano microsphere loaded magnesium matrix to obtain a precursor; and then soaking the precursor in 50mL of solution containing 3mol/L calcium chloride for 1h, taking out a sample, and freeze-drying for 48h to obtain the magnesium scaffold.
Example 2 of the present invention is: a preparation method of a magnesium stent comprises the following steps:
s1, preparing a magnesium matrix:
pure magnesium (Beijing Ring ball gold tripod science and technology Co., ltd.) was polished with 1000-grit SiC paper, followed by rinsing with deionized water for 3min, dehydrating with ethanol for 4min, and immediately drying in air to obtain a pure magnesium sample.
Under mechanical stirring, 24g of Na 3 PO 4 ·12H 2 O、3g Ca(OH) 2 Dissolving in 700mL of deionized water to obtain a solution I; 4g of Sr (OH) 2 ·8H 2 Dissolving O in 500mL of deionized water to obtain a solution II; and mixing the solution I and the solution II, and mechanically stirring for 60min to obtain the electrolyte.
The plasma electrolytic oxidation device consists of a pulse direct current power supply, a stainless steel container serving as a counter electrode and a stirring cooling system. The pure magnesium sample was connected to the anode output and immersed in the electrolyte, and the stainless steel container was connected to the cathode output of the power supply as the cathode. The stainless steel container is put into the plastic box, and water is injected between the stainless steel container and the plastic box to absorb heat.
Plasma electrolytic oxidation: constant current mode with frequency of 2000Hz, duty ratio of 20%, positive voltage of 500V, temperature of 65 deg.C, stirring, and current density of 0.02A/cm 2 Treating for 45s at a current density of 1.5A/cm 2 The treatment is carried out for 6min.
After plasma electrolytic oxidation treatment, washing for 3 times by using ethanol and deionized water, and performing room-temperature airflow drying to obtain the magnesium matrix with the surface porous structure.
S2, preparing medicine-carrying nano microspheres:
dissolving 8mg of vascular endothelial growth factor in 0.1mL of water to obtain a vascular endothelial growth factor aqueous solution; dissolving 0.4g of poly 3-hydroxybutyrate-co-3-hydroxyvalerate (molecular weight: 10 ten thousand) in 5mL of dichloromethane to obtain a poly 3-hydroxybutyrate-co-3-hydroxyvalerate solution; uniformly dispersing the vascular endothelial growth factor aqueous solution in the poly 3-hydroxybutyrate-co-3-hydroxyvalerate solution to obtain the primary emulsion.
Transferring the primary emulsion into a storage tank of an SPG membrane emulsifier, and allowing the primary emulsion to penetrate through membrane pores of the SPG membrane under the action of air/nitrogen pressure to enter 500mL of aqueous solution dissolved with 3g of polyvinyl alcohol 1788 (Mecline); stirring at 300rpm for 10h, centrifugally collecting the drug-loaded nano-microspheres, washing the drug-loaded nano-microspheres with deionized water for 4 times, and adding 50mL of deionized water to obtain a drug-loaded nano-microsphere suspension with the particle size of 300 nm-400 nm.
S3, preparing a magnesium scaffold:
and (3) soaking the magnesium matrix in 40mL of drug-loaded nano microsphere suspension at 60 ℃, and after 4h, carrying out freeze drying treatment on the sample to prepare the drug-loaded nano microsphere magnesium-loaded matrix.
Preparing a potassium alginate (viscosity: 100mpa · s-200 mpa · s) solution with the mass volume ratio of 1%, and uniformly dripping (20 uL/s) 3mL of the potassium alginate solution onto the surface of a drug-loaded nano microsphere loaded magnesium matrix to obtain a precursor; and then soaking the precursor in 50mL of solution containing 5mol/L calcium chloride for 4h, taking out a sample, and freeze-drying for 48h to obtain the magnesium scaffold.
Example 3 of the present invention is: a preparation method of a magnesium stent comprises the following steps:
s1, preparing a magnesium matrix:
pure magnesium (peak Long Hai magnesium metal processing, ltd.) was polished using 280 grit SiC sandpaper, then rinsed with deionized water for 2min, dehydrated with ethanol for 3min, and immediately dried in air to give a pure magnesium sample.
Under mechanical stirring, 20g of Na 3 PO 4 ·12H 2 O、5g Ca(OH) 2 Dissolved in 400mL to removeAdding water to obtain solution I; 9g of Sr (OH) 2 ·8H 2 Dissolving O in 800mL of deionized water to obtain a solution II; and mixing the solution I and the solution II, and magnetically stirring for 30min to obtain the electrolyte.
The plasma electrolytic oxidation device consists of a pulse direct current power supply, a stainless steel container serving as a counter electrode and a stirring cooling system. The pure magnesium sample was connected to the anode output and immersed in the electrolyte, and the stainless steel container was connected to the cathode output of the power supply as the cathode. The stainless steel container is put into the plastic box, and water is injected between the stainless steel container and the plastic box to absorb heat.
Plasma electrolytic oxidation: constant current mode, frequency 2000Hz, duty ratio 20%, positive voltage 500V, temperature 90 deg.C, stirring, and current density of 0.03A/cm 2 Treating for 65s at a current density of 0.8A/cm 2 The treatment is carried out for 20min.
After plasma electrolytic oxidation treatment, washing for 3 times by using ethanol and deionized water, and performing room-temperature airflow drying to obtain the magnesium matrix with the surface porous structure.
S2, preparing medicine-carrying nano microspheres:
dissolving 8mg of interleukin-4 in 0.1mL of water to obtain an interleukin-4 aqueous solution; dissolving 0.4g of polycaprolactone (molecular weight: 5 ten thousand) in 5mL of dichloromethane to obtain a polycaprolactone solution; and (3) uniformly dispersing the interleukin-4 aqueous solution into the polycaprolactone solution to obtain a primary emulsion.
Transferring the primary emulsion into a storage tank of an SPG membrane emulsifier, and allowing the primary emulsion to enter 400mL of aqueous solution dissolved with 6g of methyl cellulose through membrane pores of an SPG membrane under the action of air/nitrogen pressure; stirring for 12 hours at 400rpm, centrifugally collecting the drug-loaded nano-microspheres, washing the drug-loaded nano-microspheres for 5 times by deionized water, and adding 50mL of deionized water to obtain a drug-loaded nano-microsphere suspension with the particle size of 200 nm-300 nm.
S3, preparing a magnesium scaffold:
soaking a magnesium matrix in 40mL of drug-loaded nano microsphere suspension at 45 ℃, and freeze-drying a sample after 8 hours; preparing a sodium alginate (viscosity: 200mpa · s-500 mpa · s) solution with the mass-volume ratio of 0.8%, uniformly dropwise adding (20 uL/s) 3mL of the sodium alginate solution onto the surface of the drug-loaded nano microsphere loaded magnesium matrix to obtain a precursor, then soaking the precursor in 50mL of a solution containing 0.5mol/L calcium chloride for 2h, taking out a sample, and freeze-drying for 72h to obtain the magnesium scaffold.
Example 4 of the present invention is: a preparation method of a magnesium stent comprises the following steps:
s1, preparing a magnesium matrix:
pure magnesium (peak Long Hai magnesium metal processing, ltd.) was polished using 600 grit SiC sandpaper, then rinsed with deionized water for 2min, dehydrated with ethanol for 5min, and immediately dried in air to give a pure magnesium sample.
Under mechanical stirring, 12g of Na 3 PO 4 ·12H 2 O、3g Ca(OH) 2 Dissolving in 900mL of deionized water to obtain a solution I; 2g of Sr (OH) 2 ·8H 2 Dissolving O in 300mL of deionized water to obtain a solution II; and mixing the solution I and the solution II, and magnetically stirring for 55min to obtain the electrolyte.
The plasma electrolytic oxidation device consists of a pulse direct current power supply, a stainless steel container serving as a counter electrode and a stirring cooling system. The pure magnesium sample was connected to the anode output and immersed in the electrolyte, and the stainless steel container was connected to the cathode output of the power supply as the cathode. The stainless steel container is put into the plastic box, and water is injected between the stainless steel container and the plastic box to absorb heat.
Plasma electrolytic oxidation: adopting a constant current mode, the frequency is 2000Hz, the duty ratio is 20%, the positive voltage is 500V, the temperature is 55 ℃, and the current density is 0.04A/cm under stirring 2 Treating for 10s at a current density of 1A/cm 2 Treating for 15min; after plasma electrolytic oxidation treatment, washing for 3 times by using ethanol and deionized water, and performing room-temperature airflow drying to obtain the magnesium matrix with the surface porous structure.
S2, preparing medicine-carrying nano microspheres:
dissolving 5mg of bone morphogenetic protein-2 in 0.1mL of water to obtain a bone morphogenetic protein-2 aqueous solution; dissolving 0.4g of polylactic acid-glycolic acid copolymer (molecular weight: 6 ten thousand) in 5mL of chloroform to obtain polylactic acid-glycolic acid copolymer solution; uniformly dispersing the bone morphogenetic protein-2 aqueous solution in the polylactic acid-glycolic acid copolymer solution to obtain a primary emulsion.
Transferring the primary emulsion into a storage tank of an SPG membrane emulsifier, and allowing the primary emulsion to penetrate through membrane pores of the SPG membrane under the action of air/nitrogen pressure to enter 500mL of aqueous solution dissolved with 5g of gelatin; stirring at 280rpm for 8h, centrifugally collecting the drug-loaded nano-microspheres, washing the drug-loaded nano-microspheres with deionized water for 5 times, and adding 50mL of deionized water to obtain a drug-loaded nano-microsphere suspension with the particle size of 200 nm-300 nm.
S3, preparing a magnesium scaffold:
soaking a magnesium matrix in 40mL of drug-loaded nano microsphere suspension at 30 ℃, and freeze-drying a sample after 12 hours; preparing a sodium alginate (viscosity: 500mpa · s-1000 mpa · s) solution with the mass-volume ratio of 0.8%, and uniformly dropwise adding (15 uL/s) 3mL of potassium alginate solution onto the surface of the drug-loaded nano microsphere loaded magnesium matrix to obtain a precursor; and then soaking the precursor in 50mL of solution containing 3mol/L calcium nitrate for 2h, taking out a sample, and freeze-drying for 36h to obtain the magnesium stent.
Example 5 of the present invention is: a preparation method of a magnesium stent comprises the following steps:
s1, preparing a magnesium matrix:
pure magnesium (peak Long Hai magnesium metal processing, ltd.) was polished using 800 grit SiC sandpaper, then rinsed with deionized water for 3min, dehydrated with ethanol for 3min, and immediately dried in air to give a pure magnesium sample.
Under magnetic stirring, 18g of Na 3 PO 4 ·12H 2 O、1g Ca(OH) 2 Dissolving in 600mL of deionized water to obtain a solution I; 6g of Sr (OH) 2 ·8H 2 Dissolving O in 600mL of deionized water to obtain a solution II; and mixing the solution I and the solution II, and magnetically stirring for 50min to obtain the electrolyte.
The plasma electrolytic oxidation device consists of a pulse direct current power supply, a stainless steel container serving as a counter electrode and a stirring cooling system. The pure magnesium sample was connected to the anode output and immersed in the electrolyte, and the stainless steel container was connected to the cathode output of the power supply as the cathode. The stainless steel container is put into the plastic box, and water is injected between the stainless steel container and the plastic box to absorb heat.
Plasma electrolytic oxidation: constant current mode with frequency of 2000Hz, duty ratio of 20%, positive voltage of 500V, temperature of 50 deg.C, stirring, and current density of 0.01A/cm 2 Treating for 75s at a current density of 1.2A/cm 2 The treatment is carried out for 10min.
After plasma electrolytic oxidation treatment, washing for 3 times by using ethanol and deionized water, and performing room-temperature airflow drying to obtain the magnesium matrix with the surface porous structure.
S2, preparing medicine-carrying nano microspheres:
dissolving 0.25g of polylactic acid (molecular weight: 1 ten thousand) in 5mL of tetrahydrofuran to obtain a polylactic acid solution; 50mg of naringin was uniformly dispersed in the polylactic acid solution to obtain a primary emulsion.
Transferring the primary emulsion into a storage tank of an SPG membrane emulsifier, and allowing the primary emulsion to penetrate through membrane pores of the SPG membrane under the action of air/nitrogen pressure to enter 50mL of aqueous solution dissolved with 0.75g of polyvinyl alcohol 124 (avastin); stirring at 350rpm for 4h, centrifugally collecting the drug-loaded nano-microspheres, washing the drug-loaded nano-microspheres with deionized water for 3 times, and adding 50mL of deionized water to obtain a drug-loaded nano-microsphere suspension with the particle size of 50 nm-100 nm.
S3, preparing a magnesium scaffold:
and (3) soaking the magnesium matrix in 40mL of medicine-carrying nano microsphere suspension at 50 ℃, and after 20h, carrying out freeze drying treatment on the sample to prepare the medicine-carrying nano microsphere loaded magnesium matrix.
Preparing a potassium alginate (viscosity: 10-100 mpa · s) solution with the mass volume ratio of 3%, and uniformly dripping (40 uL) 3mL of the potassium alginate solution onto the surface of a drug-loaded nano microsphere loaded magnesium matrix to obtain a precursor; and then soaking the precursor in 50mL of solution containing 1.5mol/L calcium chloride for 3h, taking out a sample, and freeze-drying for 36h to obtain the magnesium scaffold.
Comparative example 1 of the present invention is: a preparation method of a magnesium stent comprises the following steps:
s1, preparing a magnesium matrix:
pure magnesium (Shanxi Wen fond of hong Fu Mg industry, ltd.) was polished with 600-grit SiC sandpaper, then rinsed with deionized water for 3min, dehydrated with ethanol for 4min, and immediately dried in air to obtain a pure magnesium sample.
Under magnetic stirring, 15g of Na 3 PO 4 ·12H 2 O、2g Ca(OH) 2 Dissolving in 500mL of deionized water to obtain a solution I; 5g of Sr (OH) 2 ·8H 2 Dissolving O in 700mL of deionized water to obtain a solution II; and mixing the solution I and the solution II, and mechanically stirring for 40min to obtain the electrolyte.
The plasma electrolytic oxidation device consists of a pulse direct current power supply, a stainless steel container serving as a counter electrode and a stirring cooling system. The pure magnesium sample was connected to the anode output and immersed in the electrolyte, and the stainless steel container was connected to the cathode output of the power supply as the cathode. The stainless steel container is put into the plastic box, and water is injected between the stainless steel container and the plastic box to absorb heat.
Plasma electrolytic oxidation: constant current mode, frequency 2000Hz, duty ratio 20%, positive voltage 500V, temperature 75 deg.C, stirring under current density of 0.02A/cm 2 Treating for 30s at a current density of 1A/cm 2 The treatment is carried out for 12min.
After plasma electrolytic oxidation treatment, washing for 3 times by using ethanol and deionized water, and performing room-temperature airflow drying to obtain the magnesium matrix with the surface porous structure.
S2, preparing a magnesium scaffold:
soaking the magnesium matrix in 40mL of aqueous solution containing 100mg of alendronate sodium at 45 ℃, and after 16h, carrying out freeze drying treatment on the sample to obtain the drug-loaded magnesium matrix.
Preparing a sodium alginate (viscosity: 100mpa · s-200 mpa · s) solution with the mass volume ratio of 2%, and uniformly dripping (50 uL/s) 3mL of the sodium alginate solution onto the surface of the drug-loaded magnesium matrix to obtain a precursor; and then soaking the precursor in 50mL of solution containing 3mol/L calcium chloride for 1h, taking out a sample, and freeze-drying for 48h to obtain the magnesium scaffold.
Comparative example 2 of the present invention is: a preparation method of a magnesium stent comprises the following steps:
s1, preparing a magnesium matrix:
pure magnesium (Shanxi Wen fond of hong Fu Mg industry, ltd.) was polished with 600-grit SiC sandpaper, then rinsed with deionized water for 3min, dehydrated with ethanol for 4min, and immediately dried in air to obtain a pure magnesium sample.
Under magnetic stirring, 15g of Na 3 PO 4 ·12H 2 O、2g Ca(OH) 2 Dissolving in 500mL of deionized water to obtain a solution I; 5g of Sr (OH) 2 ·8H 2 Dissolving O in 700mL of deionized water to obtain a solution II; and mixing the solution I and the solution II, and mechanically stirring for 40min to obtain the electrolyte.
The plasma electrolytic oxidation device consists of a pulse direct current power supply, a stainless steel container serving as a counter electrode and a stirring cooling system. The pure magnesium sample was connected to the anode output and immersed in the electrolyte, and the stainless steel container was connected to the cathode output of the power supply as the cathode. The stainless steel container is put into the plastic box, and water is injected between the stainless steel container and the plastic box to absorb heat.
Plasma electrolytic oxidation: constant current mode, frequency 2000Hz, duty ratio 20%, positive voltage 500V, temperature 75 deg.C, stirring under current density of 0.02A/cm 2 Treating for 30s at a current density of 1A/cm 2 The treatment is carried out for 12min.
After plasma electrolytic oxidation treatment, washing for 3 times by using ethanol and deionized water, and performing room-temperature airflow drying to obtain the magnesium matrix with the surface porous structure.
S2, preparing medicine-carrying nano microspheres:
dissolving 100mg of alendronate sodium in 0.1mL of water to obtain an alendronate sodium water solution; dissolving 0.5g of polylactic acid-glycolic acid copolymer (molecular weight: 3 ten thousand) in 5mL of dichloromethane to obtain polylactic acid-glycolic acid copolymer solution; uniformly dispersing the alendronate sodium aqueous solution in the polylactic acid-glycolic acid copolymer solution to obtain a primary emulsion.
Transferring the primary emulsion into a storage tank of an SPG membrane emulsifier, and allowing the primary emulsion to penetrate through membrane pores of the SPG membrane under the action of air/nitrogen pressure to enter 300mL of aqueous solution dissolved with 3g of polyvinyl alcohol 1799 (avastin); stirring for 12 hours at 320rpm, centrifugally collecting the drug-loaded nano microspheres, washing the drug-loaded nano microspheres with deionized water for 5 times, and then adding 50mL of deionized water to obtain a drug-loaded nano microsphere suspension with the particle size of 100-200 nm.
S3, preparing a magnesium scaffold:
and (3) soaking the magnesium matrix in 40mL of medicine-carrying nano microsphere suspension at 45 ℃, and after 16h, carrying out freeze drying treatment on the sample for 48h to obtain the magnesium scaffold.
Comparative example 3 of the present invention is: a preparation method of a magnesium stent comprises the following steps:
s1, preparing a magnesium matrix:
pure magnesium (Shanxi Wen fond of hong Fu Mg industry, ltd.) was polished with 600-grit SiC sandpaper, then rinsed with deionized water for 3min, dehydrated with ethanol for 4min, and immediately dried in air to obtain a pure magnesium sample.
Under magnetic stirring, 15g of Na 3 PO 4 ·12H 2 O、2g Ca(OH) 2 Dissolving in 500mL of deionized water to obtain a solution I; 5g of Sr (OH) 2 ·8H 2 Dissolving O in 700mL of deionized water to obtain a solution II; and mixing the solution I and the solution II, and mechanically stirring for 40min to obtain the electrolyte.
The plasma electrolytic oxidation device consists of a pulse direct current power supply, a stainless steel container serving as a counter electrode and a stirring cooling system. The pure magnesium sample was connected to the anode output and immersed in the electrolyte, and the stainless steel container was connected to the cathode output of the power supply as the cathode. The stainless steel container is put into the plastic box, and water is injected between the stainless steel container and the plastic box to absorb heat.
Plasma electrolytic oxidation: constant current mode, frequency 2000Hz, duty ratio 20%, positive voltage 500V, temperature 75 deg.C, stirring under current density of 0.02A/cm 2 Treating for 30s at a current density of 1A/cm 2 The treatment is carried out for 12min.
After plasma electrolytic oxidation treatment, washing for 3 times by using ethanol and deionized water, and performing room-temperature air flow drying to obtain the magnesium matrix with the surface porous structure.
S2, preparing a magnesium scaffold:
soaking the magnesium matrix with the surface porous structure in 40mL of aqueous solution containing 100mg of alendronate sodium at 45 ℃, and after 16h, carrying out freeze drying treatment on the sample for 48h to obtain the magnesium scaffold.
Comparative example 4 of the present invention is: a preparation method of a magnesium stent comprises the following steps:
s1, preparing a magnesium matrix:
pure magnesium (Shanxi Wen fond of hong Fu Mg industry, ltd.) was polished with 600-grit SiC sandpaper, then rinsed with deionized water for 3min, dehydrated with ethanol for 4min, and immediately dried in air to obtain a pure magnesium sample.
Under magnetic stirring, 15g of Na 3 PO 4 ·12H 2 O、2g Ca(OH) 2 Dissolving in 500mL of deionized water to obtain a solution I; 5g of Sr (OH) 2 ·8H 2 Dissolving O in 700mL of deionized water to obtain a solution II; and mixing the solution I and the solution II, and mechanically stirring for 40min to obtain the electrolyte.
The plasma electrolytic oxidation device consists of a pulse direct current power supply, a stainless steel container serving as a counter electrode and a stirring cooling system. The pure magnesium sample was connected to the anode output and immersed in the electrolyte, and the stainless steel container was connected to the cathode output of the power supply as the cathode. The stainless steel container is put into the plastic box, and water is injected between the stainless steel container and the plastic box to absorb heat.
Plasma electrolytic oxidation: constant current mode with frequency of 2000Hz, duty ratio of 20%, positive voltage of 500V, temperature of 75 deg.C, and stirring current density of 0.02A/cm 2 Treating for 30s at a current density of 1A/cm 2 The treatment is carried out for 12min.
After plasma electrolytic oxidation treatment, washing for 3 times by using ethanol and deionized water, and performing room-temperature airflow drying to obtain the magnesium matrix with the surface porous structure.
S2, preparing medicine-carrying nano microspheres:
dissolving 100mg of alendronate sodium in 0.1mL of water to obtain an alendronate sodium water solution; dissolving 0.5g of polylactic acid-glycolic acid copolymer (molecular weight: 6 ten thousand) in 5mL of dichloromethane to obtain polylactic acid-glycolic acid copolymer solution; uniformly dispersing the alendronate sodium aqueous solution in the polylactic acid-glycolic acid copolymer solution to obtain a primary emulsion.
Transferring the primary emulsion into a storage tank of an SPG membrane emulsifier, and allowing the primary emulsion to penetrate through membrane pores of the SPG membrane under the action of air/nitrogen pressure to enter 300mL of aqueous solution dissolved with 3g of polyvinyl alcohol 1799 (avastin); stirring for 12h at 200rpm, centrifugally collecting the drug-loaded nano-microspheres, washing the drug-loaded nano-microspheres with deionized water for 5 times, and adding 50mL of deionized water to obtain a drug-loaded nano-microsphere suspension with the particle size of 150 nm-250 nm.
S3, preparing a magnesium scaffold:
and (3) soaking the magnesium matrix in 40mL of medicine-carrying nano microsphere suspension at 45 ℃, and after 16 hours, carrying out freeze drying treatment on the sample to prepare the medicine-carrying nano microsphere loaded magnesium matrix.
Preparing a sodium alginate (viscosity: 100mpa · s-200 mpa · s) solution with the mass-volume ratio of 2%, and uniformly dripping (70 uL/s) 3mL of the sodium alginate solution onto the surface of the drug-loaded nano microsphere loaded magnesium matrix to obtain a precursor; and then soaking the precursor in 50mL of solution containing 3mol/L calcium chloride for 1h, taking out a sample, and freeze-drying for 48h to obtain the magnesium stent containing the microsphere coating.
The magnesium stent materials prepared in examples 1 to 5 and comparative examples 1 to 4 were subjected to the following performance evaluations, and the test results are shown in table 1 and fig. 1.
In vitro cytotoxicity evaluation:
the prepared magnesium bracket is taken and evaluated and scored according to the requirements of GB/T16886.5. The results are shown in Table 1.
TABLE 1 in vitro cytotoxicity scores of magnesium scaffolds prepared in examples 1-5 and comparative examples 1-4
As can be seen from the results of in vitro cytotoxicity evaluation (Table 1) of the examples and comparative examples, the scaffolds prepared by the method of the present invention were not cytotoxic.
In vitro drug release performance detection:
the magnesium scaffold materials prepared in examples 1 to 5 and comparative examples 1 to 4 were evaluated for solute release in vitro, and the results are shown in fig. 1. The evaluation method comprises the following steps: in vitro solute release experiments were performed in a constant temperature shaker at 37 ℃ and 60 rpm. 500mg of the stent was immersed in 200ml of PBS (phosphate buffered saline, pH = 7.4), the test solution was periodically collected and supplemented with an equal amount of PBS, and the collected test solution was measured for solute content by High Performance Liquid Chromatography (HPLC). And substituting the absorbance of the solute at a certain time point into a standard curve of the solute to obtain the actual released amount of the solute at the time point. The cumulative amount of solute released at this point in time is determined by dividing the actual amount by the total amount of solute loaded in the material. The results of the in vitro drug release performance measurements are shown in Table 2.
TABLE 2 in vitro drug Release Properties of magnesium stents prepared in examples 1 to 5 and comparative examples 1 to 4
As can be seen from the results of in vitro drug release performance tests (fig. 1 and table 2), both example 1 and comparative example 1 are magnesium stents loaded with alendronate sodium; however, compared with example 1, the drug of comparative example 1 is not preloaded with the polyester nanospheres, and the drug is directly loaded on the surface porous structure of the magnesium substrate and coated with the alginate coating; example 2 and comparative example 2 are both magnesium scaffolds loaded with alendronate sodium; but compared with the example 1, the comparative example 2 does not contain the alginate coating, and the drug-loaded polyester nano-microspheres are directly loaded on the surface porous structure of the magnesium matrix; example 1 and comparative example 3 are both alendronate sodium loaded magnesium stents; however, compared with example 1, the drug of comparative example 3 is not preloaded with the polyester nanospheres and does not contain the alginate coating, and the drug is directly loaded on the surface porous structure of the magnesium substrate; compared with example 1, the stents prepared in comparative examples 1 to 3 all lack the sustained-release function for the drug and have a large burst effect. Example 1 and comparative example 4 are both magnesium scaffolds loaded with alendronate sodium; however, compared with example 1, the molecular weight of the degradable polyester of the polyester nanospheres prepared in comparative example 4 is 6 ten thousand, and the drug release rate of the prepared stent is slower than that of example 1. This suggests that the drug-loaded polyester nanospheres can maintain good biocompatibility and impart controlled release function to the material drug after being compounded to the surface porous structure of the magnesium substrate, so that the material drug is more suitable for tissue repair and regeneration.
FIG. 2 is an SEM photograph of pure magnesium in example 1 of the present invention; the surface of the pure magnesium is smooth as shown in FIG. 2; FIG. 3 is an SEM photograph of a magnesium substrate in example 1 of the present invention; as can be seen from FIG. 3, the surface of the magnesium matrix after plasma oxidation treatment has a porous structure with a pore size of 500nm to 20 μm; it follows that when the drug-loaded microspheres are loaded in the pore structure, the radius of the drug-loaded microspheres is less than 400nm.
In conclusion, the magnesium scaffold has the advantages of excellent biocompatibility and bioactivity, low density, capability of promoting osteogenesis, inducing bone ingrowth and the like, and can be used as an induction template for providing structural, mechanical and biological signals to guide survival, proliferation and correct differentiation of bone-related cells. The stent drug-loaded nano-microsphere is prepared from degradable polyester, the molecular weight of the degradable polyester is 1.0-10.0 kilodalton, the mass ratio of the drug to the polyester in the drug-loaded nano-microsphere is 1:5-100, the drug release period is 14-28 days, the drug controlled release capacity is strong, and the stent drug-loaded nano-microsphere is more suitable for treating diseases such as tissue defect, bacterial infection, inflammation, tumor and the like. Through the introduction of the drug-loaded nano-microspheres and the alginate coating, the magnesium drug is endowed with a controlled release function, and the degradation of magnesium can be inhibited. The drug-loaded nano-microsphere and the magnesium matrix material have the advantages of simple combination mode, low requirement on equipment, industrialized raw materials, easily available sources, low cost and easy realization of industrialization.
While the embodiments of the present invention have been described in detail with reference to the description and the drawings, the present invention is not limited to the embodiments, and various changes can be made within the knowledge of those skilled in the art without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features of the embodiments may be combined with each other without conflict.
Claims (17)
1. A magnesium alloy composite material is characterized in that:
comprises a substrate;
drug-loaded nano microspheres are distributed on the surface of the matrix;
the matrix and the drug-loaded nano-microspheres are coated in alginate;
wherein the matrix comprises a magnesium matrix;
the magnesium substrate is of a surface porous structure, and the aperture is 500 nm-20 mu m;
the drug-loaded nano-microspheres comprise drugs and polyester nano-microspheres;
the medicine is coated in the polyester nano-microsphere;
the method for preparing the magnesium alloy composite material comprises the following steps: loading the drug-loaded nano microspheres on the surface of a matrix, and then coating the matrix with alginate; before loading the drug-loaded nano-microspheres, carrying out plasma electrolytic oxidation on the matrix; the parameters of the plasma electrolytic oxidation are as follows:
the frequency is 2000Hz; duty cycle 20%; the voltage is 500V; the temperature is 50-90 ℃; pre-oxidation current density 0.01A/cm 2 ～0.04A/cm 2 (ii) a The pre-oxidation time is 10-75 s; oxidation current 0.8A/cm 2 ～1.5A/cm 2 (ii) a The oxidation time is 6 min-20 min.
2. The magnesium alloy composite material according to claim 1, wherein: the polyester nano-microsphere is prepared from polyester.
3. A magnesium alloy composite material according to claim 2, characterized in that: the polyester includes at least one of polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, poly 3-hydroxyalkanoate, poly (3-hydroxybutyrate), poly 3-hydroxybutyrate-co-3-hydroxyvalerate, polytrimethylene carbonate and polybutylene succinate.
4. A magnesium alloy composite material according to claim 2, characterized in that: the molecular weight of the polyester is 1.0-10.0 kilodalton.
5. The magnesium alloy composite material according to claim 1, wherein: the particle size of the drug-loaded nano-microsphere is 50nm to 400nm.
6. The magnesium alloy composite material according to claim 1, wherein: the medicine comprises one of bone morphogenetic protein-2 (BMP-2), bone morphogenetic protein-7 (BMP-7), interleukin-4 (IL-4), vascular Endothelial Growth Factor (VEGF), alendronate sodium, naringin and resveratrol.
7. The magnesium alloy composite material according to claim 1, wherein: the mass ratio of the medicine to the polyester nano-microspheres is 1 to 5-100.
8. The magnesium alloy composite material according to claim 1, wherein: the release period of the medicine is 14 to 28 days.
9. The magnesium alloy composite material according to claim 1, wherein: the alginate comprises sodium alginate.
10. The magnesium alloy composite material according to claim 1, wherein: the viscosity of the alginate is 10 mPa.s-1000 mPa.s.
11. The magnesium alloy composite material according to claim 1, wherein: the plasma electrolytic oxidation comprises the following steps:
s1, carrying out surface treatment on pure magnesium to prepare a pure magnesium sample;
s2, carrying out plasma electrolytic oxidation on the pure magnesium sample in an electrolyte to prepare the magnesium matrix;
the electrolyte comprises the following raw materials in parts by weight: solution i and solution ii:
the solution I comprises the following raw materials in parts by weight: 12-14 parts of sodium phosphate, 1-5 parts of calcium hydroxide and 400-900 parts of water;
the solution II comprises the following raw materials in parts by weight: 2-9 parts of strontium hydroxide and 300-800 parts of water.
12. The magnesium alloy composite material according to claim 1, wherein: the preparation method of the drug-loaded nano-microsphere comprises an emulsion solvent volatilization method.
13. A magnesium alloy composite material according to claim 12, wherein: the emulsifying solvent volatilization method comprises the following steps:
s01, adding polyester into a solvent; preparing a polyester solution; dispersing the medicine in a polyester solution to prepare a primary emulsion;
s02, distributing the primary emulsion and a surfactant solution on two sides of the SPG membrane; stirring to obtain the drug-loaded nano-microsphere.
14. A magnesium alloy composite material according to claim 13, wherein: the surfactant includes at least one of cellulose acetate, gelatin, methyl cellulose, and polyvinyl alcohol.
15. The magnesium alloy composite material according to claim 1, wherein: the alginate is coated, and the method comprises the following steps:
s001, adding the magnesium matrix into the drug-loaded nano microsphere suspension, reacting for 4h to 20h at the temperature of 30-60 ℃, and drying after reaction to obtain the drug-loaded nano microsphere loaded magnesium matrix;
s002, preparing the alginate into an alginate solution, and dropwise adding the alginate solution to the surface of the drug-loaded nano microsphere magnesium-loaded matrix to prepare a coating precursor;
and S003, adding the coating precursor into a calcium-containing solution to react for 0.5 to 3 hours, and drying after the reaction to obtain the magnesium alloy composite material.
16. A magnesium stent characterized by: prepared from the magnesium alloy composite material of any one of claims 1 to 15.
17. Use of a magnesium scaffold according to claim 16 in the preparation of a material for tissue repair and regeneration.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04327525A (en) * | 1991-04-26 | 1992-11-17 | Kyocera Corp | Sustained release medicine-containing ceramic porous substance |
| CN102886076A (en) * | 2012-09-27 | 2013-01-23 | 深圳清华大学研究院 | Bone repair porous bracket and rapid forming method |
| CN105457104A (en) * | 2015-12-21 | 2016-04-06 | 西南交通大学 | Preparation method of bone tissue engineering porous ceramics scaffold |
| CN107970490A (en) * | 2017-12-22 | 2018-05-01 | 重庆医科大学附属永川医院 | A kind of degradable composite material for bone wound reparation and preparation method thereof |
| CN112494723A (en) * | 2020-12-03 | 2021-03-16 | 广东省医疗器械研究所 | Piezoelectric support and preparation method and application thereof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100464789C (en) * | 2005-12-22 | 2009-03-04 | 上海交通大学 | Digestive tract stent with anti-cancer medicinal particles |
| US20070259101A1 (en) * | 2006-05-02 | 2007-11-08 | Kleiner Lothar W | Microporous coating on medical devices |
| CN101239009B (en) * | 2008-01-29 | 2010-09-15 | 乐普（北京）医疗器械股份有限公司 | Controlled degradation microarc oxidized metallic support and manufacture method thereof |
| CN101721266B (en) * | 2009-12-23 | 2011-07-06 | 天津大学 | Absorbable magnesium alloy stent of anticorrosion and drug release composite coating and preparation method thereof |
| CN102397584B (en) * | 2011-11-15 | 2013-10-09 | 东南大学 | Medical magnesium alloy surface degradable composite protective film layer and preparation method thereof |
| KR101278204B1 (en) * | 2011-12-22 | 2013-06-27 | 경북대학교 산학협력단 | Method for preparing biomedical metal/alloy material with multi-drug delivery system |
| CN103566414B (en) * | 2013-08-13 | 2016-01-13 | 重庆大学 | A kind of nucleocapsid structure receives particulate coatings intravascular stent and preparation method thereof |
| US20170014548A1 (en) * | 2014-03-17 | 2017-01-19 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Magnesium/polymer composite-containing scaffolds to enhance tissue regeneration |
| CN104818414B (en) * | 2015-03-19 | 2017-08-11 | 中国科学院金属研究所 | It is a kind of with the metal bone-grafting material of loose structure and its preparation and application |
| EP3981444A1 (en) * | 2017-03-30 | 2022-04-13 | Biomet Manufacturing, LLC | Methods of modifying the porous surface of implants |
| DE102018129604B3 (en) * | 2018-11-23 | 2020-03-12 | Meotec Gmbh | Biodegradable implant that includes a coated magnesium alloy product |
| CN110629270B (en) * | 2019-09-17 | 2021-01-15 | 广东省医疗器械研究所 | Preparation method of strontium-containing biological film layer |
| CN112587731B (en) * | 2020-12-03 | 2022-06-24 | 广东省医疗器械研究所 | Composite stent and preparation method and application thereof |
-
2021
- 2021-05-17 CN CN202110534271.5A patent/CN113244446B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH04327525A (en) * | 1991-04-26 | 1992-11-17 | Kyocera Corp | Sustained release medicine-containing ceramic porous substance |
| CN102886076A (en) * | 2012-09-27 | 2013-01-23 | 深圳清华大学研究院 | Bone repair porous bracket and rapid forming method |
| CN105457104A (en) * | 2015-12-21 | 2016-04-06 | 西南交通大学 | Preparation method of bone tissue engineering porous ceramics scaffold |
| CN107970490A (en) * | 2017-12-22 | 2018-05-01 | 重庆医科大学附属永川医院 | A kind of degradable composite material for bone wound reparation and preparation method thereof |
| CN112494723A (en) * | 2020-12-03 | 2021-03-16 | 广东省医疗器械研究所 | Piezoelectric support and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| "Ca-P涂层镁合金支架负载缓释微球修复股骨缺损";卢燕勤等;《中国组织工程研究》;20181214;第23卷;第232-238页 * |
| "Corrosion behavior of porous magnesium coated by plasma electrolytic oxidation in simulated body fluid";Alireza Ghasemi et al;《Materials and Corrosion》;20190402;第70卷;第1561-1569页 * |
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